Immunopathology Part II Immune Mediated Tissue Injury


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Immunopathology Part II
Autoimmune Disease Pathology of Transplantation Laboratory evaluation of the Immune System Immunodeficiency Amyloidosis

3/24/2014

Immune Mediated Tissue Injury

ANTIGEN APC

B-CELLS

IgE and ALLERGIC DISEASE
I

ANTIBODIES and IMMUNE COMPLEXES

II, III

T-CELLS
+

+ CD4

CD8

DELAYED-TYPE HYPERSENSITIVITY

CYTOTOXICITY IV

1

3/24/2014
Autoimmunity and Autoimmune Disease

Autoimmune Disease: Single-Organ And Systemic (Multiorgan)

Organ-Specific
Hashimoto thyroiditis Autoimmune hemolytic anemia Multiple Sclerosis Autoimmune Orchitis Goodpasture Syndrome Autoimmune Thrombocytopenia Insulin Dependent Diabetes Mellitus Myasthenia Gravis Graves Disease Autoimmune Hepatitis

Systemic
Systemic Lupus Erythematosus Rheumatoid Arthritis Sjogren Syndrome Reiter Syndrome Inflammatory Myopathies Systemic Sclerosis

Mechanisms of Autoimmunity

Antinuclear Antibody IF

Homogeneous Peripheral/rim

Speckled Centromere

2

Antinuclear Antibody IF
Anti dsDNA: Crithidia lucida
Autoantibodies: LE Cell

3/24/2014
Extractable Nuclear Antigens:
“Alphabet Soup”
Anti ds-DNA (native DNA): 40-60% SLE (< 5% other) Anti-histone: 50-70% SLE (< 5% other) Anti-Smith (Sm): 20-30% SLE RNP (ribonucleoprotein):
SS-A (Ro): 70-95% SS, 30-50% SLE SS-B (La): 60-90% SS, 10-15% SLE Scl-70 (DNA topoisomerase I): 28-70% PSS
10-18% limited Scl. Anti centromere: 90% limited Scl., 22-36% PSS
Anti-Jo-1 (Histidyl tRNA synthetase): 25% myositis

Systemic Lupus Erythematosus
3

Systemic Lupus Erythematosus

A systemic autoimmune disease Incidence: 1/2500 (40/100,000) N. European

SKIN

Immune-mediated Inflammation

LUNGS, OTHER

KIDNEY

CARDIOVASCULAR

BLOOD CELLS

CNS JOINTS

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“Garbage Disposal Hypothesis”

AUTOANTIBODIES IN SLE
Antinuclear antibodies:
ANA Screen
Anti-dsDNA Anti-Sm
Antiphospholipid Antibodies
Antigens: beta-2 glycoprotein, annexin
Other Autoantibodies

Pathology of SLE: Kidney
Class I Normal (LM) Class II Mesangial Class III Focal
Proliferative Class IV Diffuse
Proliferative Class V Membranous

Pathology of SLE: Kidney

4

Pathology of SLE: Kidney

3/24/2014 Pathology of SLE: Kidney

Pathology of SLE: Kidney EM

Systemic Lupus Erythematosus Skin Involvement

Pathology of SLE: Skin

Pathology of SLE: Skin

5

Pathology of SLE:
Heart
Libman Sachs Endocarditis
Accelerated Atherosclerosis

3/24/2014 Pathology of SLE: Spleen

Systemic Lupus Erythematosus

Natural History and Prognosis:
Unpredictable course with episodic exacerbations (flares) Patterns of autoantibody expression:

Survival
1950s Current

4 yr survival 50% 15 year survival 80%

Mortality:

Bi-phasic
Early: severe inflammatory disease (lupus), or infection Late: myocardial infarction, stroke

SLE REVISED CRITERIA

1-3: SKIN:

malar rash 85% discoid rash photosensitivity

4-6: SURFACE INFLAMMATION:

7: RENAL:

proteinuria 50-70% casts

oral ulcers arthritis serositis 25-45%

8: NEUROLOGICAL: seizures 25-30% psychosis

9: HEMATOLOGIC: cytopenias 100%

10: IMMUNOLOGIC: anti dsDNA, Antiphospholipid, anti Sm

11: ANA

Systemic Lupus Erythematosus:
Treatment
Minor symptoms:
NSAIDS low dose prednisone
Moderate to Severe
Hydroxychloroquine Corticosteroids mycophenolate mophetil Azathioprine Anti B-cell agents: Rituximab
**Also: Aggressive modification of cardiac risk factors

6

Discoid Lupus
Sjogren Syndrome
Sicca syndrome Mikulicz disease

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Lupus Variants
Drug Induced “Lupus”
Drugs: hydralazine, procainamide, isoniazid, penicillamine
+ ANA may be only feature (anti-histone >95%)
+/- Skin and Multisystem involvement CNS involvement rare
Sjogren Syndrome: Salivary Gland

Sjogren Syndrome: Lymphoepithelial lesion

Sjogren Syndrome; Chronic inflammation and Atrophy

7

Sjogren Syndrome: Complications: Malignant Lymphoma

3/24/2014
Scleroderma (Progressive Systemic Sclerosis)
Diffuse Cutaneous Localized Cutaneous Limited: CREST

Nailbed Capillaroscopy

8

3/24/2014
Raynaud’s Phenomenon 9

Progressive Systemic Sclerosis
Clinical features:
Raynaud’s phenomenon Skin changes Musculoskeletal GI Pulmonary Cardiac Renal
Dermatomyositis

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Autoimmune Inflammatory Myopathies
Dermatomyositis
Heliotrope skin rash + myopathy (proximal to distal)
Children and adults affected Extra muscular disease: lung Capillaries are major target

Polymyositis
Myopathy without skin involvement Predominantly adult disease Direct cell mediated infiltration of muscle Systemic involvement: heart, lungs
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Immunopathology Part II Immune Mediated Tissue Injury